Syntheses and biological activity of amamistatin B and analogs.

Kelley A Fennell, Ute Möllmann, Marvin J Miller

Department of Chemistry and Biochemistry and Walther Cancer Center, University of Notre Dame, Notre Dame, Indiana 46556, USA.

The Journal of organic chemistry 2008 Feb 1

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Amamistatins A and B, natural products isolated from a strain of Nocardia, showed growth inhibition against three human tumor cell lines (IC(50) 0.24-0.56 microM). Structurally related mycobactins affect the growth of both mycobacterial and human cells through interference with iron chelation. To further probe the biological activity of this class of compounds, the total syntheses of amamistatin B and two analogs were completed, and the synthetic samples were screened for tumor cell growth inhibition, HDAC inhibition, and Mycobacterium tuberculosis growth inhibition. Amamistatin B (15) and diastereomer 18 were both active against MCF-7 cells (IC(50) 0.12-0.20 microM), and less so against PC-3 cells (IC(50) 8-13 microM). Amamistatin B only moderately inhibited the growth of M. tuberculosis (MIC 47 microM) but showed growth promotion of Mycobacterium smegmatis and other bacteria.

Citation

Kelley A Fennell, Ute Möllmann, Marvin J Miller. Syntheses and biological activity of amamistatin B and analogs. The Journal of organic chemistry. 2008 Feb 1;73(3):1018-24